pH-responsive shell cross-linked nanoparticles with hydrolytically labile cross-links

A pH-sensitive cross-linker was synthesized and incorporated into supramolecular block copolymer assemblies. The acetal-based degradable cross-linker was prepared from 4-methoxy-1-napthaldehyde and azidoethoxyethanol, followed by reduction. Real-time monitoring of the degradation process was accomplished by observing the UV absorbance in the region of 275-400 nm and comparing the absorbance at 350 nm. pH-sensitive shell cross-linked knedel-like (SCKs) were constructed from amphiphilic diblock copolymer PAA ₆₀-b-PS₃₀, followed by cross-linking using the acetal cross-linker. Importantly, the preparation and purification steps were performed at 0°C, and the samples were maintained at this reduced temperature. Accelerated degradation was observed at lysomal pH for this cross-linker in general, which might provide an attractive approach for controlled drug delivery.